Diabetes is a disease that afflicts close to 16 million Americans. Type I diabetes, or juvenile diabetes, is characterized by absolute insulin deficiency and dependence on exogenous insulin to sustain life. Approximately 800,000–1.6 million people have been diagnosed with type I diabetes. Type II diabetes results from a metabolic disorder in which the body does not properly use the insulin it produces. Approximately 15 million people have type II diabetes. Total cost (indirect and direct) exceeds 98 billion dollars.
Current long-term treatment of type I diabetes relies predominantly on subcutaneous injection of exogenous insulin. This treatment however does not provide optimal metabolic control, as this therapy is not able to mimic the delicate minute-by-minute modulation of insulin secretion, which normally occurs in relation to meals, exercise, etc. Even with the advent of biotechnology to produce many different types of insulin, which vary in their onset, peak, and duration of action, it is still difficult to properly control glucose levels throughout the day. When diabetics inject insulin, peripheral tissues are exposed to higher levels of insulin so that it is more difficult to properly regulate liver metabolism in these patients. Although good metabolic control with near normal glycemia has been demonstrated by using multiple (2–4) daily injections, the inconvenience of such a large number of injections precludes a widespread use of this regiment.
The most convenient, comfortable, acceptable, and easiest delivery route would be oral. The gastrointestinal (GI) mucosa offers several advantages as an administration site over other mucus membranes. These advantages include the following: (1) the oral administration route is familiar, convenient, and an accepted means of dosing for most people; (2) the GI epithelium offers a large surface area for absorption; and (3) the GI epithelium provides a close connection with a vast blood supply. Hormones, such as insulin, are administered via the subcutaneous route, because they are unable to get past the harsh environment of the upper gastrointestinal tract. Unlike subcutaneous injections, oral delivery of insulin would be able to mimic the transport of physiologic insulin from the pancreas to the hepatic portal circulation, as seen in healthy non-diabetic individuals. However, oral delivery of insulin intact is believed to be virtually impossible. No more than 0.5% of orally administered insulin is absorbed under the best experimental conditions. Even if a little of the insulin is able to miraculously pass through the upper gastrointestinal tract, the hormone is fairly large and hydrophillic, rendering it incapable of crossing through the intestinal barrier.